combination of orelabrutinib and obinutuzumab in untreated marginal zone lymphomas

Conditions: Marginal Zone Lymphoma

Summary: this is a prospective single arm phase ii study, and the purpose of this study is to evaluate the safety and efficacy of orelabrutinib combined with obinutuzumab a in untreated marginal zone lymphoma. it is planned to recruit 45 patients. the primary endpoint is the complete remission rate at 12 months.

marginal zone lymphomas (mzl) are a type of lymphoma that originates from the marginal zone tissue of the lymphoid follicles (mucosa-associated lymphoid tissue, malt), and include three subtypes: malt lymphoma, nodal mzl, and splenic mzl. for patients with marginal zone lymphoma who have indications for systemic anti-tumor treatment, therapeutic options include rituximab monotherapy or more intensive immunochemotherapy regimens in combination with bendamustine, chlorambucil, chop regimen (cyclophosphamide, vincristine, doxorubicin, prednisone), etc. this is a prospective, phase ii, single-arm clinical study to initially explore the efficacy and safety of orelabrutinib combined with obinutuzumab in patients with previously untreated marginal zone lymphoma. the patients will be treated with 6 cycles of og regimen. patients with cr/pr after 6 cycles of og treatment will be treated with 18 cycles of single-agent orelabrutinib regimen.

Eligibility criteria:
inclusion criteria: * • age ≥18 years, gender unrestricted; * histopathologically confirmed cd20-positive marginal zone lymphoma including malt, smzl, nmzl; * mzl that has progressed, recurred, or is unsuitable for local treatment after previous local therapy (local treatments include surgery, radiotherapy, helicobacter pylori treatment, hepatitis c treatment); * ecog performance status score of 0-2. * major organ functions meet the following criteria: a) complete blood count: absolute neutrophil count ≥1.5×10\^9/l, platelets ≥75×10\^9/l, hemoglobin ≥75g/l; if accompanied by bone marrow involvement, absolute neutrophil count ≥1.0×10\^9/l, platelets ≥50×10\^9/l, hemoglobin ≥50g/l; b) blood biochemistry: total bilirubin ≤1.5 times the upper limit of normal (uln), ast or alt ≤2 times uln; serum creatinine ≤1.5 times uln; serum amylase ≤uln; c) coagulation function: international normalized ratio (inr) ≤1.5 times uln. * life expectancy ≥3 months; * voluntarily sign a written informed consent form before the trial screening. exclusion criteria: * currently or previously having other malignant tumors, unless radical treatment has been performed and there is evidence of no recurrence or metastasis within the last 5 years; * lymphoma involving the central nervous system or transforming into a higher grade; * having uncontrollable or significant cardiovascular diseases, including: a) new york heart association (nyha) class ii or above congestive heart failure, unstable angina, myocardial infarction within 6 months before the first administration of the study drug, or arrhythmias requiring treatment at the time of screening, with a left ventricular ejection fraction (lvef) \&lt;50%; b) primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy); c) a history of clinically significant qtc interval prolongation, or a qtc interval \&gt;470ms in females and \&gt;450ms in males during the screening period; d) subjects with symptomatic or medication-requiring coronary artery heart disease; e) subjects with difficult-to-control hypertension (despite lifestyle improvements and the use of reasonable, tolerable, and adequate doses of one or three or more antihypertensive drugs \[including diuretics\] for more than 1 month, blood pressure is still not at the standard, or it is only effectively controlled when taking four or more antihypertensive drugs). * active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or the investigator believes there is a definite bleeding tendency; * active infection or uncontrolled hbv (positive for hbsag and/or hbcab with positive hbv dna titer), positive for hcv ab, hiv/aids, or other serious infectious diseases. * any other conditions deemed unsuitable for participation in this trial by the investigator.

Keywords: marginal zone lymphomas orelabrutinib obinutuzumab